SYNERGISTIC EFFECTS OF CHLORDANE AND TPA IN MULTISTAGE MORPHOLOGICAL TRANSFORMATION OF SHE CELLS

The cyclodiene pesticide chlordane has been reported to be a non-genot oxic carcinogen in rodents. The effects of chlordane on SHE cell trans formation were investigated in this study. It appeared that chlordane exhibited a weak transforming activity when applied repeatedly at 8 mu g/ml. No effect resulted from the combination of benzo[a]pyrene-chlor dane. In contrast, chlordane in the range 5-20 mu g/ml and 12-O-tetrad ecanoylphorbol-13-acetate (TPA) (0.1 mu g/ml) highly potentiated each other when applied sequentially. The synergistic effects could be inhi bited by dexamethasone. These results led us to study the genotoxicity of chlordane on SHE cells: no DNA adduct formation could be detected in SHE cells treated with chlordane at a concentration potentiating th e transforming effect of TPA. We also confirmed that this pesticide ma rkedly inhibited intercellular communication between SHE as well as V7 9 cells. These results support literature data on the non-genotoxicity of chlordane. Overall, this study highlights the fact that interactio n between-non genotoxic carcinogens may enhance the transformation fre quency of SHE cells. Thus, combined effects must be taken into account in the evaluation of carcinogenic risk.